# Early Rod Dysfunction Influences Cone Development in a Rhodopsin P23H Mouse Model of Retinitis Pigmentosa

## TL;DR

This study shows that cone photoreceptors in mice with a retinitis pigmentosa mutation increase in number early in life, possibly compensating for rod dysfunction.

## Contribution

The study reveals a novel compensatory increase in cone photoreceptor numbers in response to early rod dysfunction in a mouse model of retinitis pigmentosa.

## Key findings

- RhoP23H.GFP mice showed significantly increased cone photoreceptor numbers at P12, P16, and P24 compared to controls.
- Cone morphology was altered in diseased cones, suggesting developmental adaptations.
- Rhodopsin mislocalization in rod cell bodies at P12 normalized by P24 in RhoP23H.GFP mice.

## Abstract

Background/Objectives: The RhoP23H/WT mouse line is a commonly used model to study rhodopsin P23H-associated autosomal dominant retinitis pigmentosa. Previous studies in RhoP23H/WT mice have largely focused on retinal changes occurring at one month of age and later, and have indicated a compensatory thickening of inner retinal layers in response to rod degeneration. However, the effect of disease processes during early postnatal retinal development remains understudied. Methods: In this study, we investigated the retinal response to rod dysfunction during early postnatal developmental ages P8–P24 in our novel RhoP23H/WT reporter line, RhoP23H.GFP, which expresses green fluorescent protein (GFP) exclusively in cone photoreceptors. Results: Histological analysis revealed no significant difference in retinal thickness in RhoP23H.GFP mice compared to healthy controls at the ages investigated. RhoP23H.GFP retinas initially exhibited a greater mislocalization of rhodopsin to the rod cell bodies at P12, though this mislocalization normalized to wildtype by P24. Most notably, flow cytometry revealed significantly increased cone photoreceptor numbers in P12 (61%), P16 (48%), and P24 (40%) RhoP23H.GFP mice compared to wildtype controls, indicating a possible compensatory response of cone photoreceptors to rod dysfunction. Additionally, cone morphology appeared altered in diseased cones. Conclusions: Our results suggest that cones may undergo a developmental compensatory adaptation in response to rod dysfunction, providing new insights into early disease mechanisms of retinitis pigmentosa.